A New Scale Weighs Single Molecules in Real Time

Measuring the masses of tiny objects takes a tiny scale. To that end, researchers from the California Institute of Technology and Leti, an institute at the French Alternative Energies and Atomic Energy Commission, have built a new mass-identifying device with dimensions measuring in the nanometers and microns. The apparatus can determine the masses of individual molecules in real time—the first device of its kind to do so—the researchers reported in a study published in September in Nature Nanotechnology. (Scientific American is part of Nature Publishing Group.)

The heart of the scale is a beam of silicon just a few hundred nanometers wide that vibrates at two tones simultaneously. (A nanometer is one billionth of a meter.) Tiny arms at either end of the beam convert the resonator's vibrations into an electrical signal via a phenomenon known as the piezoresistive effect. A single molecule landing on the beam is enough to shift the frequency of the two tones downward, changing the electrical resistance of the device's arms in a way that depends on the mass of the particle.

As a demonstration, the researchers performed mass spectrometry—identifying the various particles in a mixture by their masses—on collections of gold nanoparticles five nanometers in diameter, as well as on the antibody molecule immunoglobulin M. As study co-author Michael Roukes, a Caltech physicist, notes, previous resonator devices needed hundreds of identical molecules to make a measurement. “We couldn't actually know, molecule by molecule, what their mass was,” he says.

The new, more sensitive version should allow researchers to perform mass spectrometry to identify the various particles within a mixed sample. A mass spectrometer capable of identifying single protein molecules could prove invaluable for proteomics—teasing out the function and structure of different proteins within a cell or tissue. “If we can do it one by one, now we can start looking at arbitrarily complex mixtures of different things,” Roukes says.